A variety of pathological processes can lead to valvular malfunction in a mammalian cardiovascular system. This is particularly true of the valves found in the heart which are essential for controlling the flow of blood. Natural tissue heart valves are thin, fibrous structures having substantial tensile strength. Primarily composed of collagen proteoglycans and small amounts of elastin, natural tissue heart valves are flexible and variably compliant yet durable. Among other causes, heart valve deterioration may be brought about by genetic diseases of the connective tissues where crosslinking of collagen is impaired, by rheumatic fever, and by a variety of infectious diseases. Valve dysfunction is usually associated with degenerative changes of the valve tissue that require surgical correction or replacement with a bioprosthetic device. While artificial or mechanical bioprostheses have been used for some time they continue to present problems including clot formation and excessive turbulence following implantation.
These and other deficiencies associated with mechanical valvular prosthetics have spurred the development of heart valve substitutes incorporating naturally-occurring valve structures. In one form, these prostheses are constructed using allografts, that is tissue from human corpse aortic valves. However, a shortage of human donors and the possibility of pathogenic contamination have limited the use of cadaveric allografts. Accordingly, xenogeneic valvular prostheses, i.e., those based on tissue from a species other than human, have become the principal form of valve replacement implanted today. Typically, xenogeneic valve prostheses are manufactured from bovine pericardium or porcine heart valves which closely resemble human valve structures and, less frequently, from membranes of dura mater (cranial membranes) or fascia lata (connective tissue) from cattle.
Yet, when tissue is transplanted directly from the source organism, it rapidly deteriorates in the hostile physiological environment of the host. It was quickly established that "fixation" of the natural tissue is critical to the operation of implanted tissue valves for prolonged periods. Glutaraldehyde or polyepoxy compounds have become the most common agents for fixing tissue used in valvular prosthetics. In addition to arresting autolysis, the fixing agents produce a stronger, more resilient material having improved tensile properties due to increased collagen crosslinking. Crosslinking of the collagen molecules also increases their resistance to proteolytic cleavage thereby rendering the treated tissue less susceptible to enzymatic degradation in the body. Further, fixing agents have the ability to reduce the antigenicity of xenograft tissue to a level at which it can be implanted into the heart without provoking a significant immunological reaction from the host.
From a clinical standpoint, long term tissue damage in fixed valvular prosthetics is primarily the consequence of destruction of the collagen fiber network, calcification, and shearing forces occurring from obstructions in the valve orifice area. Calcification is the single largest cause of failure in biological valvular prosthetics, whether they incorporate pericardial valve leaflets or natural valve structures. Commonly, the buildup of calcium requires the replacement of the prosthetic device after a few years, subjecting the patient to substantial risk.
Conventional fixation techniques tend to increase the rate of calcification by making the valve tissue uniformly stiff and noncompliant. Like tanned shoe leather, uniformly stiff valve tissue and, in particular, valve leaflets lead to an uneven distribution of applied stress. Unlike living valve tissue which is variably compliant, that is having radially asymmetric flexing characteristics along the leaflet body, uniformly stiff fixed leaflets do not distribute dynamic strain homogeneously throughout the tissue matrix. As with a shoe, the irregular distribution of force and the resulting stress points produce localized tearing, cracking and abrasion. The accumulation of calcium is accelerated where the non-compliant connective tissue is subjected to repetitive motions that increase the amount of matrix disruption and detached fibers. In addition to enhancing the rate of calcification due to the disruption of the tissue matrix at these stress points, inhibition of the variably compliant motions of the prosthetic leaflets can lead to stenosis, increased fluid turbulence, and an elevated rate of tissue abrasion in and around the prosthetic device.
Accordingly, while prior art fixation techniques substantially improve the characteristics of the treated tissue, problems still remain with respect to shape retention, elasticity, strength, calcification and durability. Simple immersion of the valve tissue into a bath of fixative subjects it to random hydrostatic or hydrodynamic forces resulting in uniformly stiff leaflets that are not variably compliant. The uniform stiffness and decreased compliance promotes incorrect architecture and undesirable strain concentrations throughout the tissue when introduced into a physiological setting.
In order to overcome these limitations, several attempts have been made to fix the valvular tissue under pressure. Fixing the valvular structure under constant pressure can reinforce its natural configuration and help assure the proper coaptation of the valve leaflets following implantation. Examples of constant pressure fixation processes may be found in U.S. Pat. Nos. 3,983,581, 4,035,849 and 4,050,893 in which porcine valves are fixed in glutaraldehyde with the valve cusp held in a closed position by applying hydraulic pressure to the ventricular or outflow side of the valve. The selected pressure is uniformly maintained over the entire surface of the ventricular side of the valve establishing a pressure differential across the width of the leaflet.
Despite improvements in terms of the initial architectural configuration, tissue leaflets treated under pressurized conditions are still uniformly stiff rather than variably compliant. As with unpressurized fixation techniques, the elimination of variable flexibility increases the uneven stress on the tissue matrix which, in turn, enhances the rate of calcification. Again the resulting calcium crystal formation interferes with the natural collagen biomechanics, hemodynamic flow and detracts from the ability of the valve to maintain its precise architecture during years of service.
Accordingly, it is an object of the present invention to produce a natural tissue valve prosthesis with variably compliant leaflets having improved hemodynamic performance.
It is another object of the present invention to produce a natural tissue valve prosthesis wherein the valve leaflets are resistant to calcification.
It is still another object of the present invention to provide a natural tissue prosthetic devices having enhanced durability and a correspondingly longer performance profile following implantation.